Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson's disease

Jining Medical College, Jining, China.
Brain research (Impact Factor: 2.84). 07/2009; 1286:25-31. DOI: 10.1016/j.brainres.2009.06.060
Source: PubMed


The high-fat ketogenic diet (KD) leads to an increase of blood ketone bodies (KB) level and has been used to treat refractory childhood seizures for over 80 years. Recent reports show that KD, KB and their components (d-beta-hydroxybutyrate, acetoacetate and acetone) have neuroprotective for acute and chronic neurological disorders. In our present work, we examined whether KD protected dopaminergic neurons of substantia nigra (SN) against 6-hydroxydopamine (6-OHDA) neurotoxicity in a rat model of Parkinson's disease (PD) using Nissl staining and tyrosine hydroxylase (TH) immunohistochemistry. At the same time we measured dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. To elucidate the mechanism, we also measured the level of glutathione (GSH) of striatum. Our data showed that Nissl and TH-positive neurons increased in rats fed with KD compared to rats with normal diet (ND) after intrastriatal 6-OHDA injection, so did DA and its metabolite DOPAC. While HVA had not changed significantly. The change of GSH was significantly similar to DA. We concluded that KD had neuroprotective against 6-OHDA neurotoxicity and in this period GSH played an important role.

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    • "Infusion of β-hydroxybutyric acid in mouse protects from ageing the dopaminergic neurodegeneration and motor deficits induced by MPTP [49]. Moreover KD protected dopaminergic neurons of the substantia nigra against 6-hydroxydopamine neurotoxicity in a rat model of Parkinson disease [95]. VanItaille et al. [96] demonstrated that in humans, able to prepare a “hyperketogenic” diet at home and adhere to it for 28 days, the high level of KB was related to an improvement in the Unified Parkinson's Disease Rating Scale scores. "
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    • "in 1 - methyl - 4 - phenyl - 1 , 2 , 3 , 6 - tet - rahydropyridine ( MPTP ) in culture ( Koustova et al . , 2003 ) . This neuroprotective effect of the KD is also observed in vivo . The damage induced on the dopaminer - gic neurons in the SN and dopamine levels in the striatum by 6 - hydroxydopamine ( 6 - OHDA ) is reduced when rats are fed a KD ( Cheng et al . , 2009 ) . A recent study indicates that valproic acid , another antiepileptic drug , also exerts a"
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